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Biomedical subjects

D Wong

Publications and source records attributed to D Wong.

At least 19 recordsLinked to original sources

Histological findings of a choroidal neovascular membrane removed at the time of macular translocation in a patient previously treated with intravitreal bevacizumab treatment (Avastin).

AIM: To report the findings in a patient treated by repeated intravitreal bevacizumab (Avastin) injections, followed by macular relocation and excision of subfoveal choroidal neovascular membrane (CNV). METHODS: Histopathological evaluation of the CNV specimen, including immunohistochemical assessment. RESULTS: During surgical excision, the CNV seemed to be avascular and its underlying bed did not bleed. Histopathological examination revealed that the CNV comprised avascular fibrous subretinal tissue containing fibroblastic retinal pigment epithelial (RPE) cells, fragments of irregular thickened Bruch's membrane and fibrotic choroidal tissue containing some medium-sized vessels but no choriocapillaris. CONCLUSIONS: The development of an RPE tear during the course of Avastin treatment may reflect contraction of the avascular subretinal tissue, whereas the lack of capillaries in both choroidal and subretinal components may be caused by the increased access of Avastin to the choriocapillaris in the presence of the RPE tear.

Aged↗

Tadalafil is efficacious in Black American and Hispanic men with erectile dysfunction: results from multiple observations in men with erectile dysfunction in national tadalafil study in the US (MOMENTUS).

To show that tadalafil is efficacious in Black American and Hispanic men with erectile dysfunction (ED) and efficacy is noninferior to that in Caucasian men. Multiple observations in men with ED in national tadalafil study in the US, a multicenter, open-label study, assessed the efficacy of tadalafil 20 mg taken as needed (maximum one dose/day before sexual activity) for 12 weeks by patients with ED in various populations. This analysis focuses on three groups: Caucasian (Reference group), Black American, and Hispanic men. Primary measurement of efficacy was change from baseline in erectile function (EF) domain of the International Index of Erectile Function (IIEF) and the primary analysis was whether efficacy in Black American and Hispanic groups was noninferior to efficacy in the Caucasian group. Secondary efficacy measures included sexual encounter profile (SEP), IIEF intercourse satisfaction (IS) and overall satisfaction (OS) domains, Global Assessment Question (GAQ), and Psychological and Interpersonal Relationship Scale (PAIRS). Safety was assessed from adverse events (AEs) reported by all enrolled patients. The increase in IIEF EF domain score (>or=9.5) from baseline for each group was statistically significant (P<0.001) and clinically relevant. Efficacy of tadalafil in Black American and Hispanic patients was noninferior to the Caucasian group. IS and OS domains of IIEF had a statistically significant increase from baseline (P<0.001). Change from baseline in positive responses to SEP questions for each group was significant (P<0.001). At least 77% of intercourse attempts were successful over various time intervals up to 36 h postdose. At least 88% of patients in the various groups had a positive response to GAQ1. Improvement from baseline in Sexual Self-Confidence and Spontaneity domains of PAIRS was statistically significant (P<0.001). A low number of AEs and a low AE-related discontinuation rate (2.3%) were reported in all groups. Tadalafil 20 mg was as efficacious in Black American and Hispanic men with ED as in Caucasian patients and was well tolerated.

Adult↗

Comparison of Luneau SA disposable and Goldmann applanation tonometer readings.

PURPOSE: To test the agreement of intraocular pressure (IOP) measurements made with Luneau SA applanators and Goldmann applanator. MATERIALS AND METHODS: A single-blind crossover trial. IOPs were measured in both eyes of subjects with both applanators. Type of applanator was alternated to eliminate systematic bias. Multiple observers were used. Observers were blind to the scale while performing measurements but not to the type of applanator used. The appearance of the meniscus was assessed semiquantitatively. All measurements were combined and presented in a Bland-Altman plot. RESULTS: A total of 140 eyes of 79 subjects were tested by seven observers. The range of measurements was 6-45 mmHg (mean 17.8 mmHg) for the Goldmann applanator. On average, the Luneau SA applanator (range of measurements 4-36 mmHg) gave a measurement of 2.35 mmHg less than the Goldmann standard. The standard deviation of these differences was 2.13 mmHg, giving an upper 95% confidence limit of 6.53 mmHg and a lower 95% confidence limit of -1.83 mmHg. The measurements agreed in only 24 out of 140 instances. In 28 eyes, the disposable tonometer end point was difficult to assess owing to excessively thick rings. Linear extrapolation suggests an increase in difference with increasing IOP. CONCLUSION: The inter-head inaccuracy, tendency to underestimate IOP, and lack of systematic inaccuracy make a corrective algorithm impossible to formulate. The range of variation between the Luneau SA disposable applanator and the Goldmann standard is sufficiently large to influence clinical management decisions. We speculate that one explanation is the interaction of the tonometer with the tear film, making end point determination difficult. Further research is being undertaken.

Cross-Over Studies↗

A next generation, pilot-scale continuous sterilization system for fermentation media.

A new continuous sterilization system was designed, constructed, started up, and qualified for media sterilization for secondary metabolite cultivations, bioconversions, and enzyme production. An existing Honeywell Total Distributed Control 3000-based control system was extended using redundant High performance Process Manager controllers for 98 I/O (input/output) points. This new equipment was retrofitted into an industrial research fermentation pilot plant, designed and constructed in the early 1980s. Design strategies of this new continuous sterilizer system and the expanded control system are described and compared with the literature (including dairy and bio-waste inactivation applications) and the weaknesses of the prior installation for expected effectiveness. In addition, the reasoning behind selection of some of these improved features has been incorporated. Examples of enhancements adopted include sanitary heat exchanger (HEX) design, incorporation of a "flash" cooling HEX, on-line calculation of F(o) and R(o), and use of field I/O modules located near the vessel to permit low-cost addition of new instrumentation. Sterilizer performance also was characterized over the expected range of operating conditions. Differences between design and observed temperature, pressure, and other profiles were quantified and investigated.

Bioreactors↗

Do antiviral CD8+ T cells select hepatitis C virus escape mutants? Analysis in diverse epitopes targeted by human intrahepatic CD8+ T lymphocytes.

Hepatitis C virus (HCV) is a variable RNA virus that can readily establish persistent infection. Cellular immune responses are important in the early control of the virus. Evidence from animal models suggests that mutation in epitopes recognized by CD8+ T lymphocytes may play an important role in the establishment of persistence but in human persistent infection, equivalent evidence is lacking. We investigated this by analysing a unique resource: viruses from a set of chronically HCV-infected individuals in whom the CD8+ T-cell responses in liver had previously been accurately mapped. Virus was sequenced in seven individuals at 10 epitopes restricted by 10 human leucocyte antigen (HLA) molecules. Two main patterns emerged: in the majority of epitopes sequenced, no variation was seen. In three epitopes, mutations were identified which were compatible with immune escape as assessed using phylogenetic and/or functional studies. These data suggest that - even where specific intrahepatic T cells are detectable - many epitopes do not undergo mutation in chronic human infection. On the contrary, virus may escape from intrahepatic CD8+ T-cell responses in a 'patchy' manner in certain specific epitopes. Furthermore, longitudinal studies to identify the differences between 'selecting' and 'nonselecting' intrahepatic CD8+ T-cell responses are needed in HCV infection.

CD8-Positive T-Lymphocytes↗

Profiles of executive function in parents and siblings of individuals with autism spectrum disorders.

Delineation of a cognitive endophenotype for autism is useful both for exploring the genetic mechanisms underlying the disorder and for identifying which cognitive traits may be primary to it. This study investigated whether first-degree relatives of individuals with autism spectrum disorders (ASDs) demonstrate a specific profile of performance on a range of components of executive function (EF), to determine whether EF deficits represent possible endophenotypes for autism. Parents and siblings of ASD and control probands were tested on EF tasks measuring planning, set-shifting, inhibition and generativity. ASD parents showed poorer performance than control parents on a test of ideational fluency or generativity, and ASD fathers demonstrated a weakness in set-shifting to a previously irrelevant dimension. ASD siblings revealed a mild reduction in ideational fluency and a weakness in non-verbal generativity when compared with control siblings. Neither ASD parents nor siblings displayed significant difficulties with planning or inhibition. These results indicated that the broad autism phenotype may not be characterized primarily by impairments in planning and cognitive flexibility, as had been previously proposed. Weaknesses in generativity emerged as stronger potential endophenotypes in this study, suggesting that this aspect of EF should play a central role in cognitive theories of autism. However, discrepancies in the EF profile demonstrated by parents and siblings suggest that factors related to age or parental responsibility may affect the precise pattern of deficits observed.

Adult↗

Secondary paracentral retinal holes following internal limiting membrane removal.

AIM: To report on a new postoperative finding after delamination of the internal limiting membrane (ILM) for the treatment of different macular pathologies. METHODS: Seven patients are described with paracentral retinal holes, all located temporally to the macula, which developed after pars plana vitrectomy and uncomplicated ILM removal for cystoid macular oedema (n = 3), macular pucker (n = 3), and macular hole (n = 1) with the use of indocyanine green (n = 4), trypan blue (n = 1), triamcinolone acetonide (n = 1), or without dye (n = 1). CONCLUSION: The use of dyes has been incriminated in causing iatrogenic damage to the retina. In this series, the new observation of retinal holes in the macular area is thought to be related to the removal of the ILM itself. The authors speculate that ILM delamination may cause a retinal weakening by Müller cell damage; this may be followed by a structural breakdown and, consequently, hole formation.

Adult↗

Denaturing HPLC for high-throughput screening of rifampicin-resistant Mycobacterium tuberculosis isolates.

OBJECTIVE: To evaluate the use of denaturation high-performance liquid chromatography (dHPLC) as a rapid method to detect rifampicin (RMP) resistance based on mutations in the rpoB gene in a high-volume laboratory setting. METHODS: A total of 132 RMP-resistant Mycobacterium tuberculosis strains with different rpoB mutation were used to optimise the running condition of dHPLC as a pilot study. A blind correlation study was subsequently done between dHPLC and in vitro RMP susceptibility tests on 3167 M. tuberculosis strains in a high-throughput clinical setting. RESULTS: In the pilot study, rpoB mutation could be detected on 116/132 (87.9%) RMP-resistant strains by dHPLC. In the second phase of the study, 84/3107 (2.7%) clinical M. tuberculosis isolates were RMP-resistant. The sensitivity and specificity of dHPLC in the prediction of RMP resistance were 70/84 (83.3%) and 70/77 (91.0%), respectively. The specificity became 100% when 511 Leu to Pro mutation was excluded from the RMP resistance-related genetic changes. CONCLUSION: In the detection of RMP resistance in a high-throughput laboratory setting, dHPLC has been demonstrated to be rapid, simple, workable, automatable and inexpensive in terms of running costs and the labour involved.

Bacterial Proteins↗

Acute and reversible micrographia in a patient possibly due to cerebral ischaemia.

We report a patient who developed acute and reversible micrographia, presumably due to cerebral ischaemia, on a background of mutism following a pharyngo-laryngectomy 10 years earlier. Magnetic resonance (MR) imaging showed chronic small vessel disease without evidence of an acute ischaemic lesion on diffusion-weighted sequences. Our patient's micrographia improved significantly within 12 days of symptom onset. The MR imaging was performed within 5 days of symptom onset, suggesting that the lesion was either too small for detection or had resolved on diffusion-weighted sequences.

Aged↗

Variable assortative mating in replicate mating trials using Drosophila melanogaster populations derived from contrasting opposing slopes of 'Evolution Canyon', Israel.

Significant assortative mating in laboratory studies has been previously shown between two populations of Drosophila melanogaster collected from micro-climactically contrasting and opposing slopes of 'Evolution Canyon' (Lower Nahal Oren, Israel; Korol et al., 2000). Coupled with evidence that the two populations are adapted to their respective environments, this has been suggested as a rare example of ongoing behaviourally mediated speciation occurring in the face of gene flow. Reproductive isolation between these populations, however, has never been confirmed by replicate experiments in an independent laboratory. For this reason, we tested recent collections of these populations for premating isolation in both the original (Haifa) and a new (Burnaby) laboratory under a variety of experimental protocols. Although non-random mating was found in the majority of trials conducted in Haifa, we were unable to replicate these strong results in Burnaby. Most notably, we failed to detect assortative mating in four separate double choice experiments. Significant non-random mating was detected, however, in three of six single choice experiments in Burnaby, suggesting that the populations are behaviourally differentiated in some manner. Why nonrandom mating was weaker in Burnaby than Haifa is not understood, but suggests that assortative mating may be sensitive to unknown environmental factors.

Animals↗

Optical coherence tomography in photodynamic therapy for subfoveal choroidal neovascularisation secondary to age related macular degeneration: a cross sectional study.

AIMS: To introduce new terminology and validate its reliability for the analysis of optical coherence tomography (OCT) scans, compare clinical detection of cystoid macular oedema (CMO) and subretinal fluid (SRF) with OCT findings, and to study the effect of photodynamic therapy (PDT) on the foveal morphology. METHODS: Patients with subfoveal, predominantly classic choroidal neovascularisation (CNV) secondary to age related macular degeneration (AMD) undergoing PDT were evaluated with refraction protocol best corrected logMAR visual acuity (VA), slit lamp biomicroscopy, stereoscopic fluorescein angiography (FFA), and OCT. New terminologies introduced to interpret the OCT scans were: neuroretinal foveal thickness (NFT), bilaminar foveal thickness (BFT), outer high reflectivity band thickness (OHRBT), intraretinal fluid (IRF), subretinal fluid (oSRF), and vitreomacular hyaloid attachment (VMHA). RESULTS: Fifty six eyes of 53 patients were studied. VA was better in eyes with a thinner outer high reflectivity band (OHRBT) (p = 0.02) and BFT (p = 0.05). BFT was less in eyes that had undergone a greater number of PDT treatments (p = 0.04). There was poor agreement between OCT and clinical examination in the detection of CMO and subretinal fluid (kappa = 0.289 and kappa = 0.165 respectively). To validate the interpretation and measurements on OCT, two groups of 20 scans were analysed by two independent observers. There was good agreement between the observers in the detection of IRF, oSRF, and VMHA (p<0.001). Measurements of NFT and BFT had a high reproducibility, and of OHRBT reproducibility was low. CONCLUSIONS: New terminology has been introduced and tested. OCT appears to be superior to clinical examination and FFA in the detection of CMO. In this study, better vision was associated with a thinner OHRBT and/or the absence of SRF giving insight into the biological effect of PDT.

Aged↗

Visual loss following removal of intraocular silicone oil.

AIM: To investigate the cause of visual loss following removal of intraocular silicone oil in patients who underwent vitrectomies for retinal detachment or giant retinal tear. METHODS: The clinical records of three cases with visual loss following removal of silicone oil were reviewed. Investigations carried out included fundus fluorescein angiogram, optical coherence tomography, and electrophysiological studies. RESULTS: Visual acuities dropped from 6/9 to 6/36 in two cases and 6/24 to 3/24 in the third. None of the three cases had macula detachment at any stage. Fundus fluorescein angiogram and optical coherence tomography were normal in all cases. Pattern electroretinogram showed reduced amplitudes of the P50 and N95 components. Multifocal electroretinogram indicated a selective damage to the central part of the macula. CONCLUSIONS: The results suggest that the abnormality arises predominantly in the central part of the macula, especially the outer and middle layers. However, the exact mechanism still remains obscure.

Adult↗